The accident between a late-model Ford Falcon travelling west on the Princes Highway and a Transit van travelling east happend at Larpent, 10 kilometres west of Colac between Larpent Road and Nalangil Road, about 1.15pm.

The 70-year-old male driver of the Falcon died at the scene while his 12-year-old female passenger was airlifted to the Royal Children's Hospital.

Police said the pair in the Falcon were not related and all three people involved in the accident were from Melbourne.

A hospital spokeswoman said the girl had multiple injuries. She underwent surgery last night and was reported to be in a serious but stable condition.

It is believed she has leg and abdominal injuries.

The 33-year-old male driver of the Transit van was airlifted to The Alfred hospital, where a spokesman said last night he was in a stable condition.

Sergeant Shane Howard of Colac police said while the death of anyone on the roads was a tragedy, emergency services were pleased to see two survivors.

"Any high-speed collision is going to result in massive trauma and to have anyone survive is a good result. Unfortunately someone has died, which is tragic," he said.

CFA, SES, ambulance and police crews attended the accident which closed the straight stretch of highway for six hours.

A police spokeswoman said Major Collision Investigators attended the scene.

"At this stage the circumstances surrounding the collision are unclear," she said.

Police will prepare a report for the coroner.

The fatal collision comes after a teenager and truck driver were killed yesterday when their vehicles crashed and burst into flames south of Horsham .

The truck driver, a Horsham man aged in his mid-40s, and a 19-year-old car driver were killed in the head-on collision on the Western Highway near Dadswells Bridge just after 8am, a Victoria Police spokeswoman said.

Thirty minutes after the Horsham crash, a man had to be placed in an induced coma while being freed from his car after being trapped for more than an hour in Melbourne's outer south-east.

The 40-year-old's car collided with the pylon of an overhead sign near the Princes Highway exit on the South Gippsland Freeway in Hallam about 8.30am.